The regulation of acyl-CoA dehydrogenases in adipose tissue by rosiglitazone.
The acyl-CoA dehydrogenases (ACADs), which catalyze the rate-limiting step in the mitochondrial beta-oxidation spiral, were investigated in white adipose tissue (WAT) of C57Bl/6 mice treated with 10 mg/kg/day rosiglitazone. Rosiglitazone was also administered to PPAR-alpha knockout mice. ACAD abundance and activity were determined using western blotting and an ACAD enzyme activity assay. Rosiglitazone increased ACAD activity in both epididymal and inguinal WAT but not in brown adipose tissue, liver, or muscle. Given the known function of PPAR-alpha in regulating the expression of ACAD genes in liver, it was hypothesized that PPAR-alpha may be involved in upregulating the ACADs during rosiglitazone-mediated adipose tissue remodeling. However, the effect of rosiglitazone on adipose tissue ACAD activity was the same in wild-type and PPAR-alpha knockout mice. In conclusion, rosiglitazone increases expression and activity of ACAD enzymes in WAT independently of PPAR-alpha.
Goetzman
Eric S
ES
Department of Pediatrics, School of Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. eric.goetzman@chp.edu
D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D004822:Epididymis / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D045162:Thiazolidinediones; D000077154:Rosiglitazone; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain